1. Field of the Invention
This invention relates generally to viscous medical preparations, and, more specifically, to viscous solutions containing glycated chitosan and dried films prepared therefrom.
2. Background
Viscoelastic substances are used routinely in the medical field for protection and manipulation of tissues and maintenance of spaces. Viscoelastic materials prepared from various naturally occurring substances or synthesized in the laboratory include sodium hyaluronate, chondroitin sulfate and combinations thereof, cellulosic materials, and polymers based on acrylamide. Previously used viscoelastics have disadvantages which include allergic reactions, neurotoxic impurities, inadequate viscosity or viscoelasticity; unacceptable levels of particulate materials; gels or bulky polymer chains which might enter and plug fluid meshworks; procurement difficulties due to the use of animal derived raw materials; and excessive cost. Materials which are not broken down and absorbed in vivo also generally require that they be irrigated from the body.
It is thus an object of the present invention to provide improved viscoelastic preparations which are far less subject to the above-noted disadvantages.
In connection with the present invention there are provided preparations containing glycated chitosan in a physiologically compatible carrier. Such preparations possess useful viscoelastic properties, are absorbable by hydrolysis in vivo and, surprisingly, are endowed with antibacterial qualities. Dry films prepared from glycated chitosan solutions are also provided.
Chitosan is a deacetylated derivative of chitin, a plentiful substance readily isolated from the shells of crustaceans such as crab, lobster and shrimp. Glycated chitosan refers to products resulting from the reaction between free amino groups of chitosan and carbonyl groups of reducing monosaccharides and/or oligosaccharides.
The preferred viscoelastic preparations comprise 1.0-12.0 percent by weight of glycated chitosan in an aqueous solution, depending upon the desired physical properties. The otherwise free amino groups of the chitosan polymer are preferably 30-90% glycated, and the molecules possess an average molecular weight of between 100,000 and 2,000,000 Daltons, and, most preferably between 100,000 and 1,000,000 Daltons. The inventive viscoelastic solutions are of a viscosity greater than 10,000 centistokes (one centistoke=a resistance to flow of 1 mm/sec) and, most preferably between 10,000 and 80,000 centistokes, measured at 25xc2x0 C. A particularly preferred form of glycated chitosan for use in the inventive preparations is galacto-chitosan.
The inventive solutions and films are useful in a myriad of medical applications, including, for example, as viscoelastic ophthalmic agents and as drug carriers for medicaments for topical application to the eye; antimicrobial coatings for use on adhesive strips or burn and wound dressings; tissue void replacement materials; lavage solutions; tissue separation films, mouth rinses; facial lotions; or as hand and body disinfectants.
In an alternate embodiment, certain low viscosity preparations are provided for use as ophthalmic wetting agents for topical application to the eye and as drug carriers for medicaments for topical application to the eye. The preparations are particularly useful when combined with certain medicaments or drugs, which are entrapped in the glycated chitosan preparations. Since the preparations are broken down over time by enzymes in eye secretions, they have the characteristic of sustained release. For use as a wetting agent or eye drop, the inventive preparations comprise less than 1.0, and preferably 0.1-0.5, percent by weight of glycated chitosan in a physiologically compatible aqueous solution, while possessing 30-90%, preferably 60%, glycation of the otherwise free amino groups of the chitosan polymer and having a viscosity in the range from about 10 centistokes to about 100 centistokes.
Especially for ophthalmic preparations, the glycated chitosan is preferably contained in an aqueous solution having a pH between 5.5 and 7.5, and, most preferably, in a dilute slightly acidic aqueous solution having a pH between 6.3 and 7.
A better understanding of the present invention, its several aspects, and its objects and advantages will become apparent to those skilled in the art from the following detailed description, wherein there is described the preferred embodiment of the invention, simply by way of illustration of the best mode contemplated for carrying out the invention.